Dataset Information

Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer.

ABSTRACT: Endometrial cancer (EC) is one of the most frequently diagnosed gynecological cancers worldwide, and its prevalence has increased by more than 50% over the last two decades. Despite the understanding of the major signaling pathways driving the growth and metastasis of EC cells, clinical trials targeting these signaling pathways in human patients have reported poor outcomes. Heterogeneous nature of EC is suspected to be one of the key reasons for the failure of targeted therapies. However, no study so far has explored EC heterogeneity within the same patient at the proteomic level. In this study, we isolated proteins from tumor tissue samples obtained from different sites of EC from individual patients (~2-4 samples/patient). We then performed a SWATH-based comparative proteomic analysis, using liquid chromatography-tandem mass spectrometry (LC-MS/MS), to profile the protein content of different areas within EC tissue. Our results highlighted an average of 1424 unique proteins in 20 patient-derived EC tissues with a confidence corresponding to a false discovery rate below 1%. We have identified protein biomarkers that differentiate between premenopausal vs postmenopausal cancer, macroscopic vs microscopic tumor, and more vs less invasive cancer, and DNA mismatch repair defective vs intact tumor. Furthermore, the data revealed a list of unique proteins that, for the same patient, exist only in a single EC location but are not present in other locations within the same tumor. Overall, our proteomic analysis highlighted that tumor tissue samples collected from different sites of EC within the same patient can harbor diverse protein profiles. Importantly, this study sets the foundation for further investigations into the mechanisms of endometrial heterogeneity and some of the proteins identified here may represent potential novel EC drug targets.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Uterine Endometrium, Endometrium

DISEASE(S): Endometrial Cancer

SUBMITTER: Muhammad Fairuz Jamaluddin

LAB HEAD: Pradeep Tanwar

PROVIDER: PXD031784 | Pride | 2022-10-14

REPOSITORIES: Pride

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Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer.

Jamaluddin M Fairuz B MFB Ko Yi-An YA Ghosh Arnab A Syed Shafiq M SM Ius Yvette Y O'Sullivan Rachel R Netherton Jacob K JK Baker Mark A MA Nahar Pravin P Jaaback Kenneth K Tanwar Pradeep S PS

Cell reports. Medicine 20220913 9

Endometrial cancer is one of the most frequently diagnosed gynecological cancers worldwide, and its prevalence has increased by more than 50% over the last two decades. Despite the understanding of the major signaling pathways driving the growth and metastasis of endometrial cancer, clinical trials targeting these signals have reported poor outcomes. The heterogeneous nature of endometrial cancer is suspected to be one of the key reasons for the failure of targeted therapies. In this study, we p ...[more]

PMID: 36103879

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Project description:Endometrial cancer (EC) is the most common female genital malignancy and the fourth most common cancer in women in the developing world1. EC has been traditionally classified into two main groups with different clinical, pathological and molecular features2,3. Type I or endometrioid endometrial carcinomas (EECs) account for about 75% of the cases and are typically estrogen-related and low-grade tumors with good prognosis that coexist or are preceded by endometrial hyperplasia, mainly diagnosed in perimenopausal women. In contrast, type II or non-endometrioid endometrial carcinomas (NEECs) are high-grade aggressive tumors associated with endometrial atrophy and poor prognosis, unrelated to estrogen and diagnosed in older women. These comprise several histological subtypes, being the most common the serous carcinomas (SEC)4. In recent years numerous large-scale studies of primary endometrioid and serous tumors have been performed5, revealing new mutated genes and establishing a new molecular subclassification based on the results obtained by The Cancer Genome Atlas (TCGA) consortium6, which implies different clinical outcomes. More recently, the genomic evolution of EC has been analyzed through a comparative study of samples from endometrial atypical hyperplasia, primary tumors and paired metastases7, revealing the presence of intratumor heterogeneity as previously described in primary EC and other tumor types8,9. However an in-depth study considering multiple regions from primary tumor and paired metastases has not been performed up to now to our knowledge. Here we analyze by whole-exome sequencing (WES), massive parallel targeted sequencing and array comparative genomic hybridization (aCGH) the clonal evolution and intratumor heterogeneity of 7 endometrioid and 3 serous metastatic endometrial carcinomas. Different locations from the primary tumor as well as from their paired metastases were included in the study, allowing the reconstruction of the spatial and temporal phylogenetic evolution of the tumor. Different phylogenetic evolution patterns were identified, independently of the classical histological or molecular classification of the tumor, although similar patterns were found in ovarian metastasis and recurrent disease.

			Action	DRS
	190107_Fairuz_Library.mgf	Mgf
	190107_Fairuz_Library_1_.mzid.gz	Mzid
	ANE_Patient_1.wiff	Wiff
	ANE_Patient_1.wiff.scan	Wiff
	ANE_Patient_10.wiff	Wiff

Dataset Information

Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer.

Dataset's files

Publications

Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer.

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